Title
Stability of Carboplatin and Oxaliplatin in their Infusion Solutions is Due to Self-Association
Document Type
Article
Date
2011
Keywords
Anti-cancer agents; Aqueous solutions; Association constant; Association equilibria; Carboplatin; Drug concentration; Electrosprays; Long term stability; Monomeric forms; Oxaliplatin; Self-associations; Shelf life
Disciplines
Chemistry
Description/Abstract
Carboplatin and oxaliplatin are commonly used platinum anticancer agents that are sold as ready-to-use aqueous infusion solutions with shelf lives of 2 and 3 years, respectively. The observed rate constants for the hydrolysis of these drugs, however, are too large to account for their long shelf lives. We here use electrospray-trap mass spectrometry to show that carboplatin and oxaliplatin are self-associated at concentrations in their ready-to-use infusion solutions (∼27 mM and 13 mM, respectively) and, as expected, when the drug concentration is reduced to more physiologically relevant concentrations (100 μM and 5 μM, respectively) the association equilibrium is shifted in favor of the monomeric forms of these drugs. Using 1H NMR we measure the intensity of the NH resonance of the two symmetry-equivalent NH 3 molecules of carboplatin, relative to the intensity of the γ-methylene CH resonance, as a function of total drug concentration. Then, by fitting the data to models of different molecularity, we show that the association complex is a dimer with a monomer-dimer association constant of K (M -1) = 391 ± 127. The work presented here shows that carboplatin and oxaliplatin mainly exist as association complexes in concentrated aqueous solution, a property that accounts for the long term stability of their ready-to-use infusion solutions, and that these association complexes may exist, to some extent, in the blood after injection.
Recommended Citation
Di Pasqua, Anthony J.; Kerwood, Deborah J.; Shi, Yi; Goodisman, Jerry; and Dabrowiak, James C., "Stability of Carboplatin and Oxaliplatin in their Infusion Solutions is Due to Self-Association" (2011). Chemistry - All Scholarship. 29.
https://surface.syr.edu/che/29
Source
local input
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Additional Information
Copyright 2011 Dalton Transactions. This article may be downloaded for personal use only. Any other use requires prior permission of the author and Dalton Transactions.